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Early diagnosis and treatment of gastric precancerous lesions (GPL) are key factors for reducing the incidence and morbidity of gastric cancer. The study is aimed at examining GPL in mice induced by N-methyl-N-nitroso-urea (MNU) and to illustrate the underlying mechanisms of tumorigenesis. In this study, we utilized an in vivo MNU-induced GPL mouse model, and histopathological changes of the gastric mucosa were observed by hematoxylin and eosin (H&E-stain) and alcian blue (AB-PAS-stain). The level of miR-194-5p in the gastric mucosa was determined by real-time polymerase chain reaction. We used transmission electron microscopy to observe the effects of MNU on gastric chief cells and parietal cells. We performed immunohistochemical detection of HIF-1α, vWF, Ki-67, and P53, while the changes in the protein expression of key genes in LKB1-AMPK and AKT-FoxO3 signaling pathways were detected by western blot analysis. We demonstrated that the miR-194-5p expression was upregulated under hypoxia in GPL gastric tissues, and that a high miR-194-5p expression level closely related with tumorigenesis. Mechanistically, miR-194-5p exerted the acceleration of activities related to metabolic reprogramming through LKB1-AMPK and AKT-FoxO3 pathways. Furthermore, similar to miR-194-5p, high expression levels of AMPK and AKT were also related to the metabolic reprogramming of GPL. Moreover, we revealed the correlation between the expression levels of miR-194-5p, p-AMPKα, p-AKT, and FoxO3a. These findings suggest that miR-194-5p/FoxO3 pathway is important for the reversal of metabolic reprogramming in GPL. Thus, exploring strategies to regulate the miR-194-5p/FoxO3a pathway may provide an efficient strategy for the prevention and treatment of GPL.

Parietal cells of the gastric mucosa contain a complex and extensive secretory membrane system that harbors gastric H+, K+-adenosine triphosphatase (ATPase), the enzyme primarily responsible for gastric lumen acidification. Here, we describe the characterization of mice deficient in the H+, K+-ATPase α subunit (Atp4a−/−) to determine the role of this protein in the biosynthesis of this membrane system and the biology of the gastric mucosa. Atp4a−/− mice were produced by gene targeting. Wild-type (WT) and Atp4a−/− mice, paired for age, were examined at 10, 12, 14 and 16 weeks for histopathology, and the expression of mucin 2 (MUC2), α-methylacyl-CoA racemase (AMACR), Ki-67 and p53 proteins was analyzed by immunohistochemistry. For further information, phosphoinositide 3-kinase (PI3K), phosphorylated-protein kinase B (p-AKT), mechanistic target of rapamycin (mTOR), hypoxia-inducible factor 1α (HIF-1α), lactate dehydrogenase A (LDHA) and sirtuin 6 (SIRT6) were detected by Western blotting. Compared with the WT mice, hypochlorhydric Atp4a−/− mice developed parietal cell atrophy and significant antral inflammation (lymphocyte infiltration) and intestinal metaplasia (IM) with elevated MUC2 expression. Areas of dysplasia in the Atp4a−/− mouse stomach showed increased AMACR and Ki-67 expression. Consistent with elevated antral proliferation, tissue isolated from Atp4a−/− mice showed elevated p53 expression. Next, we examined the mechanism by which the deficiency of the H+, K+-ATPase α subunit has an effect on the gastric mucosa. We found that the expression of phosphorylated-PI3K, p-AKT, phosphorylated-mTOR, HIF-1α, LDHA and SIRT6 was significantly higher in tissue from the Atp4a−/− mice compared with the WT mice (P

Gastric cancer, one of the most common types of cancers, develops over a series of consecutive histopathological stages. As such, the analysis and research of the gastric precancerous lesions (GPLs) play an important role in preventing the occurrence of gastric cancer. Ginsenoside Rg3 (Rg3), an herbal medicine, plays an important role in the prevention and treatment of various cancers. Studies have demonstrated a correlation between glycolysis and gastric cancer progression. Herein, the aim of the present study was to clarify the potential role for glycolysis pathogenesis in Rg3-treated GPL in Atp4a−/− mice. The GPL mice model showed chronic gastritis, intestinal metaplasia, and more atypical hyperplasia in gastric mucosa. According to the results of HE and AB-PAS staining, it could be confirmed that GPL mice were obviously reversed by Rg3. Additionally, the increased protein levels of PI3K, AKT, mTOR, HIF-1α, LDHA, and HK-II, which are crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis in the model group, were downregulated by Rg3. Meanwhile, the miRNA-21 expression was decreased and upregulated by Rg3. Furthermore, the increased gene levels of Bcl-2 and caspase-3 were attenuated in Rg3-treated GPL mice. In conclusion, the findings of this study imply that abnormal glycolysis in GPL mice was relieved by Rg3 via regulation of the expressions of PI3K, AKT, mTOR, HIF-1α, LDHA, HK-II, and miRNA-21. Rg3 is an effective supplement for GPL treatment and can be harnessed to inhibit proliferation and induce apoptosis of GPL cells.

For the abandoned quarry complex rock slope project, the slope stability calculation is always the key technical problem, but due to the complex geological conditions and other factors, it makes the calculation of 3D modeling and the stability of the slope geological body and structure of the division, rock unit has always been the difficult problems in the field. This paper proposes a new method based on the rock mass structure combined with the degree of rock mass element, and then FLAC 3D, Midas GTS three-dimensional numerical calculation software are used, structure and surface topography in the slope, the slope surface fault, soft interlayer, complex geological 3D modeling, overcomes the problem of modeling of complex geological body, and the factors of rainfall, earthquake effect of the slope are consider for stability calculation, the calculation result is consistent with the reality, it has certain directive significance to the abandoned quarry re-greening slope stability analysis.

Due to the high steep rock slope stability analysis its complex geological conditions and other factors, its stability calculation has been a technical problems the field of slope engineering, in this paper, 3D finite element calculation software Midas GTS for side slope surface topography and slope internal faults, weak structural plane of complex three-dimensional geological modeling, it overcomes the complex slope geological modeling problem and simulates rainfall, earthquakes and other factors affecting the stability on the slope, calculated results more in line with reality, and the software calculates is in accordance with fact, it provides a useful reference for slope engineering.

The prediction of ground collapse caused by subway shield construction has been an important technical problem in urban subway shield construction, if the ground collapse could be pre-estimated, it could be able to take appropriate precautionary measures in advance to avoid the occurrence of ground surface settlement before the project construction, but it’s difficult to predict and calculate the settlement accurately. This paper analyzed main causes of ground collapse caused by shield construction, summarized the influence of several important parameters to surface settlement and then Midas GTS 3D numerical simulation software was used to simulate shield construction process and calculate ground surface settlement, to calculate stress, strain and displacement of overlying strata above the shield driving machine, obtained calculated values of surface settlement to predict ground collapse. Practice has proved that this pre-estimation new technology is in accordance with fact, it provides a useful reference for subway shield construction project.

Biomass burning (BB) in Southeast Asia (Indochina and southern China) occurs frequently in March and April every year. The burning plume is ordinarily transported eastward by the prevailing westerly, further affecting downstream air quality in East Asia. In this study, atmospheric aerosols were collected at the downstream Lulin Atmospheric Background Station (LABS, 2862 m a.s.l., central Taiwan) from April 2003 to April 2009. Results show that monthly means of PM2.5 were highest during the BB period, especially in March. The PM2.5 mean for BB activity was 17.5 μg m−3, while the daily PM2.5 mean can sometimes be above 40 μg m−3. The background PM2.5 level in free troposphere of the West Pacific was at 3.7 ± 1.8 μg m−3. This mean is roughly the same regardless of the air masses moving from China, Pacific Ocean, and South China Sea toward LABS. In addition, the highest PM2.5 level occurred in 2004, making it the most active year of BB for the whole observation period. Greater amounts of nitrate and potassium ions were observed in the PM2.5 collected during the BB period compared to the non-BB (NBB) period. Linear regression analysis on PM2.5 water-soluble ions shows a moderate correlation (R2 = 0.59) between non-sea-salt potassium and nitrate ions during the BB period. Furthermore, for all trajectory source origins, ammonium ion had the best correlation (R2 = 0.84) with non-sea-salt sulfate when the air masses were influenced by anthropogenic sources during the NBB period. The enhancement ratios of nitrate ion during the BB period could reach 6.7 and 9.7 relative to air masses from the BB source region and from the pristine area during the NBB period, respectively. During the study period, ammonia gas was found to be insufficient to neutralize sulfuric and nitric gases. Therefore, most aerosols were more acidic than basic. Our long-term observation of atmospheric aerosols with inter-annual variability is valuable in providing data for verifying BB source inventory and model performance in East Asia.

To enhance a machine’s ability for a precision machining task, an efficient compensation scheme that takes all error sources into account is needed. In this study, an effective static/quasi-static error compensation system composed of an interpolation algorithm based on shape functions for error prediction, and a recursive software compensation procedure, was developed. The new error prediction scheme is efficient enough to be implemented on-line, taking into consideration the fact that the machine structure is non-rigid. In addition, an automatic NC code converting software was also developed so that the developed system could be applied to practical machining for CNC multi-axis machines. To verify the algorithm and system, cutting experiments were conducted, and the results have shown the success of the proposed error compensation system.

Thermal deformations cause 40-70% error during the manufacturing process for the machine tools. In order to improve the accuracy of the machine tools, this study proposes a hybrid model, which predicts thermal deformation by combining an ARIMA and a feed-forward neural network (FNN) models. The genetic algorithm (GA) method is used to optimize this prediction model. The GA is used to search the optimal normalization coefficients, number of ARMA outputs and number of hidden neurons of FNN. It can reduce the network size and improve the propagation accuracy. In this study, comparisons between conventional FNN and the proposed hybrid model with or without using GA. The compared results show that the proposed hybrid model has better accuracy than the conventional FNN model and most accurate can be obtained by the proposed hybrid using GA. The predicted results, the hybrid model with GA can reduce the thermal deformation to 2 /spl mu/m.